title: A novel factor, Tmem176b, induced by activin-like kinase 2 signal promotes the differentiation of myoblasts into osteoblasts.
abstract: Previous studies have suggested some interactions between muscle tissues and bone metabolism. The constitutively activating mutation (R206H) of the BMP type I receptor, activin-like-kinase 2 (ALK2), causes fibrodysplasia ossificans progressiva (FOP), which is characterized by extensive ossifications within muscle tissues. In the present study, we revealed that Tmem176b mRNA levels were upregulated by stable transfection of ALK2 (R206H) in mouse myoblastic C2C12 cells. Transient Tmem176b overexpression elevated levels of osteoblast differentiation markers, such as Osterix and alkaline phosphatase, as well as mineralization in C2C12 cells. In addition, Tmem176b overexpression elevated the levels of these markers in mouse osteoblastic MC3T3-E1 cells. On the other hand, Tmem176b overexpression suppressed the levels of myogenic markers, such as MyoD and myogenin in C2C12 cells, although it did not affect the levels of chondrogenic markers, such as type II and X collagens. In conclusion, the present study is the first to demonstrate that Tmem176b induces the differentiation of myoblasts into an osteoblast lineage.
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Ohnohigashi, Osakasayama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Ohnohigashi, Osakasayama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kawao
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Ohnohigashi, Osakasayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Ohnohigashi, Osakasayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Ohnohigashi, Osakasayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kaji
mesh_terms: D030201:Activin Receptors, Type I / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D054338:Cell Transdifferentiation / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C552366:Tmem176B protein, mouse; D030201:Activin Receptors, Type I; C498943:Acvr1 protein, mouse